PUBLICATION

CD4-Transgenic Zebrafish Reveal Tissue-Resident Th2- and Regulatory T Cell-like Populations and Diverse Mononuclear Phagocytes

Authors
Dee, C.T., Nagaraju, R.T., Athanasiadis, E.I., Gray, C., Fernandez Del Ama, L., Johnston, S.A., Secombes, C.J., Cvejic, A., Hurlstone, A.F.
ID
ZDB-PUB-161007-34
Date
2016
Source
Journal of immunology (Baltimore, Md. : 1950)   197(9): 3520-3530 (Journal)
Registered Authors
Gray, Caroline, Hurlstone, Adam, Johnston, Simon
Keywords
none
MeSH Terms
  • Animals
  • Animals, Genetically Modified
  • Cell Differentiation
  • Cells, Cultured
  • Fish Diseases/immunology*
  • Gills/immunology
  • Interleukin-13/metabolism
  • Interleukin-4/metabolism
  • Intestinal Mucosa/immunology*
  • Macrophages/immunology*
  • Mammals
  • Melanoma/immunology*
  • Mononuclear Phagocyte System
  • Neoplasms, Experimental
  • T-Lymphocytes, Regulatory/immunology*
  • Th2 Cells/immunology*
  • Zebrafish/immunology*
PubMed
27694495 Full text @ J. Immunol.
Abstract
CD4+ T cells are at the nexus of the innate and adaptive arms of the immune system. However, little is known about the evolutionary history of CD4+ T cells, and it is unclear whether their differentiation into specialized subsets is conserved in early vertebrates. In this study, we have created transgenic zebrafish with vibrantly labeled CD4+ cells allowing us to scrutinize the development and specialization of teleost CD4+ leukocytes in vivo. We provide further evidence that CD4+ macrophages have an ancient origin and had already emerged in bony fish. We demonstrate the utility of this zebrafish resource for interrogating the complex behavior of immune cells at cellular resolution by the imaging of intimate contacts between teleost CD4+ T cells and mononuclear phagocytes. Most importantly, we reveal the conserved subspecialization of teleost CD4+ T cells in vivo. We demonstrate that the ancient and specialized tissues of the gills contain a resident population of il-4/13b-expressing Th2-like cells, which do not coexpress il-4/13a Additionally, we identify a contrasting population of regulatory T cell-like cells resident in the zebrafish gut mucosa, in marked similarity to that found in the intestine of mammals. Finally, we show that, as in mammals, zebrafish CD4+ T cells will infiltrate melanoma tumors and obtain a phenotype consistent with a type 2 immune microenvironment. We anticipate that this unique resource will prove invaluable for future investigation of T cell function in biomedical research, the development of vaccination and health management in aquaculture, and for further research into the evolution of adaptive immunity.
Genes / Markers
Figures
Show all Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping